Association of promoter variants in the α7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia
Association of promoter variants in the α7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia
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DOI：
10.1001/archpsyc.59.12.1085
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发表时间：
2002-12-01
影响因子：
--
通讯作者：
Freedman, R
中科院分区：
文献类型：
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作者：
Leonard, S;Gault, J;Freedman, R
背景：通过15q14的遗传连锁和生化数据，α - 7神经元烟碱乙酰胆碱受体亚基基因（CHRNA7）已被认为是精神分裂症和该疾病中发现的听觉感觉加工缺陷的候选基因。与对照组相比，精神分裂症患者的几个脑区CHRNA7表达减少。本研究对精神分裂症患者和对照组的CHRNA7核心启动子区进行了DNA序列分析。方法：采用单链构象多态性分析和DNA测序对CHRNA7基因核心启动子进行突变筛选。样本包括来自166个精神分裂症家庭和165个对照组的受试者。对照组没有当前或过去精神病的证据，并记录了听觉诱发电位。结果：在精神分裂症患者和对照组中，CHRNA7核心启动子均存在多个多态性模式。多态性的功能分析表明转录减少。功能性启动子变异在精神分裂症患者中的流行率在统计学上高于对照组。在对照组中，α 7启动子多态性的存在与P50听觉诱发电位反应抑制失败有关。结论：虽然不能排除与其他遗传改变的连锁不平衡，但本研究中发现的CHRNA7核心启动子变异可能与精神分裂症的共同病理生理特征有关。
Background: The alpha7 neuronal nicotinic acetylcholine receptor subunit gene (CHRNA7) has been implicated as a candidate gene for schizophrenia, and for an auditory sensory processing deficit found in the disease, by both genetic linkage at 15q14 and biochemical data. The expression of CHRNA7 is reduced in several brain regions in schizophrenic subjects compared with control subjects. This study presents DNA sequence analysis of the core promoter region for CHRNA7 in schizophrenic and control subjects.Methods: Single-strand conformation polymorphism analysis and DNA sequencing were used for mutation screening of the core promoter in the CHRNA7 gene. The sample included subjects from 166 schizophrenic families and 165 controls. Controls had no evidence of current or past psychosis and had auditory evoked potentials recorded.Results: Multiple polymorphic patterns were identified in the CHRNA7 core promoter in both schizophrenic and control subjects. Functional analysis of polymorphisms indicated that transcription was reduced. The prevalence of functional promoter variants was statistically greater in schizophrenic subjects than in the controls. Presence of an alpha7 promoter polymorphism in controls was associated with failure to inhibit the P50 auditory evoked potential response.Conclusions: Although linkage disequilibrium with other genetic alterations cannot be excluded, the CHRNA7 core promoter variants, found in this study, may contribute to a common pathophysiologic feature of schizophrenia.